This Program Project proposes to examine the functional of critical regulatory molecules in the formation of cartilage and bone and the role of a specific class of extracellular matrix (ECM) proteins in the function of cartilage and bone and the role of a specific class of extracellular matrix (ECM) proteins in the function of cartilage and bone. The program will provide important and novel information about the roles of the transcription factors Sox9 and Cbfa2 in chondrogenesis, about the role of Bone Morphogenetic Proteins in Somite, Cartilage and Bone development and about the function of Small Leucine-Rich Proteoglycans and their interactions with other ECM components in cartilage and bone. A large portion of the application proposes to utilize gene-targeting and transgenic approaches to better understand the function of these proteins in intact mice and embryos. The strengths of the Program are based on the productivity and expertise of the participating investigators and their interactions during the period of the current P011, on the interactive nature of the individual projects, on the essential support provided by the cores, and on other complementary projects ongoing in the laboratories of the project leaders. The anticipated advances in the molecular and cellular biology of skeletal development and function could not be achieved by individual projects. This Program Project should provide a more rational basis for the understanding of both genetic and acquired diseases of cartilage and bone.